Researchers differ over Zocor study

Side effects, few benefits seen with higher doses for heart attack victims

August 31, 2004|By David Kohn | David Kohn,SUN STAFF

A new study looking at aggressive attempts to lower cholesterol in patients who had just suffered heart attacks generated a dispute yesterday as top researchers disagreed sharply over the results.

The study's authors concluded that high doses of the cholesterol-lowering drug Zocor helped heart attack patients. But in an editorial accompanying the paper in the Journal of the American Medical Association, cardiologist Dr. Steven Nissen argued that the results of the study showed no benefit.

"Even though I'm one of the biggest advocates of statin use, you have to tell it like it is," said Nissen, a researcher at the Cleveland Clinic.

Known as the A to Z Trial, the study could have an impact on the $25 billion annual market for statins, a class of drugs that can lower levels of LDL, or "bad" cholesterol, reducing the risk of heart attacks and other problems. More than 1 million Americans suffer heart attacks each year.

Lipitor, made by Pfizer Inc., is the top seller, with $10 billion in sales last year, followed by Merck's Zocor, which had half that.

The paper was presented yesterday at the European Society of Cardiology conference in Munich, Germany, and will appear in the latest issue of the Journal of the American Medical Association.

Researchers looked at 4,497 heart attack patients over four years, from 1999 to 2003. About half were treated with 40 milligrams of Zocor for 30 days, then 80 milligrams, the top recommended dose, thereafter. The rest received a placebo for four months, then 20 milligrams of Zocor.

The study's authors and Merck, which funded the trial, agreed that the trial showed no statistically significant benefit, but argued that the data showed a "favorable trend."

"It didn't work out as well as we had hoped, but that doesn't mean it didn't work out well," said the study's lead author, Dr. James de Lemos, a cardiologist at University of Texas Southwestern Medical Center.

The apparent lack of benefit related in part to the higher rate of side effects when patients took Zocor at higher doses. A handful of patients experienced muscle damage, an uncommon but well-known risk of statins.

Dr. David Bilheimer, a vice president for medical affairs at Merck, portrayed the disagreement over the study as a difference of emphasis. Nissen judged it stringently, he said.

"I would give [the study] an incomplete grade. I wouldn't flunk it." Bilheimer said.

The results of the A to Z trial were somewhat surprising, given that two earlier studies found that intensive statin treatment was safe and effective. Those studies used Lipitor.

De Lemos and others in the study suggested that the outcomes might stem from differences among the study populations. The two previous studies took place in the United States, while the A to Z Trial drew subjects from around the world.

But Nissen ascribed the lack of benefit to Zocor itself.

"They took a good drug, and they pushed it to beyond its safe limits," said Nissen, who suggested in his editorial that Lipitor might be better at cutting arterial inflammation, a key problem for many heart patients.

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